Advanced prostate cancers that progress to tumor metastases are often considered incurable or difficult to treat. The etiology of prostate cancers is multi-factorial. Among other factors, de-regulation of calcium signals in prostate tumor cells mediates several pathological dysfunctions associated with tumor progression. Calcium plays a relevant role on tumor cell death, proliferation, motility-invasion and tumor metastasis. Calcium controls molecular factors and signaling pathways involved in the development of prostate cancer and its progression. Such factors and pathways include calcium channels and calcium-binding proteins. Nevertheless, the involvement of calcium signaling on prostate cancer predisposition for bone tropism has been relatively unexplored. In this regard, a diversity of mechanisms triggers transient accumulation of intracellular calcium in prostate cancer cells, potentially favoring bone metastases development. New therapies for the treatment of prostate cancer include compounds characterized by potent and specific actions that target calcium channels/transporters or pumps. These novel drugs for prostate cancer treatment encompass calcium-ATPase inhibitors, voltage-gated calcium channel inhibitors, transient receptor potential (TRP) channel regulators or Orai inhibitors. This review details the latest results that have evaluated the relationship between calcium signaling and progression of prostate cancer, as well as potential therapies aiming to modulate calcium signaling in prostate tumor progression.

Oxidative stress is a biological imbalance that contributes to cellular damage and is a major driver of aging and age-related disorders, prompting the search for natural antioxidant agents. Our study is a phytochemical, electrochemical, and biological characterization of the antioxidant potential of aqueous extracts from aerial parts of A. occidentale—leaves, bark, fruit, and cashew nuts—traditionally used in folklore medicine. Extracts were analyzed using FT-IR spectroscopy, GC × GC-TOFMS, polyphenol quantification, and antioxidant capacity assays (ABTS, FRAP, DPPH). Biological activity was tested in different mice and human cell lines (SH-SY5Y, MEF, ARPE-19, and HLECs). Aqueous extracts from the leaves and bark of A. occidentale exhibited significantly higher antioxidant activity compared to those from the fruit and cashew nut. These extracts showed elevated polyphenol content and strong performance in antioxidant capacity assays. In vitro, leaf and bark extracts enhanced cell viability under H₂O₂-induced oxidative stress, preserved mitochondrial membrane potential, and upregulated cytoprotective genes (HMOX1, NQO1, GCLC, and GCLM) in multiple cell lines. In contrast, fruit and nut extracts showed minimal antioxidant activity and no significant gene modulation. Our findings underscore the therapeutic potential of A. occidentale leaf and bark extracts as effective natural antioxidants and support their further development as candidates for phytotherapeutic interventions.

Advanced prostate cancer preferential metastasis to bone is associated with osteomimicry. MINDIN is a secreted matrix protein upregulated in prostate tumors that overexpresses bone-related genes during prostate cancer progression. Na+/H+ exchanger regulatory factor (NHERF-1) is a scaffold protein that has been involved both in tumor regulation and osteogenesis. We hypothesize that NHERF-1 modulation is a mechanism used by MINDIN to promote prostate cancer progression. We analyzed the expression of NHERF-1 and MINDIN in human prostate samples and in a premetastatic prostate cancer mouse model, based on the implantation of prostate adenocarcinoma TRAMP-C1 (transgenic adenocarcinoma of the mouse prostate) cells in immunocompetent C57BL/6 mice. The relationship between NHERF-1 and MINDIN and their effects on cell proliferation, migration, survival and osteomimicry were evaluated. Upregulation of MINDIN and downregulation of NHERF-1 expression were observed both in human prostate cancer samples and in the TRAMP-C1 model. MINDIN silencing restored NHERF-1 expression to control levels in the mouse model. Stimulation with MINDIN reduced NHERF-1 expression and triggered its mobilization from the plasma membrane to the cytoplasm in TRAMP-C1 cells. MINDIN-dependent downregulation of NHERF-1 promoted tumor cell migration and proliferation without affecting osteomimicry and adhesion. We propose that MINDIN downregulates NHERF-1 expression leading to promotion of processes involved in prostate cancer progression.

Oxidative stress is a biological imbalance that contributes to cellular damage and is a major driver of aging and age-related disorders, prompting the search for natural antioxidant agents. Our study is a phytochemical, electrochemical and biological characterization of antioxidant potential of aqueous extracts from aerial parts of A. occidentale—leaves, bark, fruit, and cashew nuts- traditionally used in folklore medicine. Extracts were analyzed using FT-IR spectroscopy, GC×GC-TOFMS, polyphenol quantification and antioxidant capacity assays (ABTS, FRAP, DPPH). Biological activity was tested in different mice and human cell lines (SH-SY5Y, MEF, ARPE-19 and HLEC). Aqueous extracts from the leaves and bark of A. occidentale exhibited significantly higher antioxidant activity compared to those from the fruit and cashew nut. These extracts showed elevated polyphenol content and strong performance in antioxidant capacity assays. In vitro, leaf and bark extracts enhanced cell viability under H₂O₂-induced oxidative stress, preserved mitochondrial membrane potential and upregulated cytoprotective genes (HMOX1, NQO1, GCLC, and GCLM) in multiple cell lines. In contrast, fruit and nut extracts showed minimal antioxidant activity and no significant gene modulation. Our findings underscore the therapeutic potential of A. occidentale leaf and bark extracts as effective natural antioxidants and support their further development as candidates for phytotherapeutic interventions.